Complex HIV Treatments Demand Greater MD Expertise

Complex HIV Treatments Demand Greater MD Expertise

SAN FRANCISCO--As AIDS has become a chronic disease, not
necessarily a fatal one, HIV-infected patients are increasingly
turning to family physicians and other primary care providers for
medical care. And such providers are getting on-the-job experience in
delivering a very complex therapy--antiretroviral drugs.

"Not every primary care doctor will do antiretroviral therapy,
and not all should. But were now being called on to be AIDS
experts," Bruce Soloway, MD, said at the American Academy of
Family Physicians 1998 Scientific Assembly. "We need to focus
not only on understanding HIV and treating symptoms early but also on
managing risk for the disease."

AIDS statistics tell the story. Between 1995 and 1997, for example,
AIDS deaths in New York City dropped 60% to 65%. "We now know
that the more intense the treatment--the more drugs used--the lower
the death rate," said Dr. Soloway, vice president of the
Institute for Family Health, New York City.

The turnaround in AIDS treatment--moving from single treatments to
combinations of drugs--stems from the work of Dr. David Ho, of the
Aaron Diamond AIDS Research Center, New York, showing that HIV can
reproduce itself at an enormously high rate--10 billion new viral
particles per day. These replications are a constant source of
genetic diversity, producing strains resistant to single therapies
such as zidovudine (Retrovir, AZT).

New combinations of powerful drugs, including the protease
inhibitors, however, successfully suppress viral replication and the
evolution of resistant strains. Yet weak antiretroviral therapy is
surprisingly worse than no treatment at all.

"It is too weak to stop the virus from reproducing but strong
enough to exert selective pressure that favors resistant
strains," Dr. Soloway said. With no treatment, the virus
continues to replicate but does not produce resistant strains.

A major problem with antiretroviral therapy is getting patients to
adhere to it, he said. Many patients are taking 15 to 20 pills a day
as therapy, and suffering serious side effects, such as elevated
cholesterol, that may demand even more drugs. But when patients miss
doses, or stop taking some of their drugs, they are in real danger.
"Thats when resistant strains crop up," he said. And
some patients already have highly resistant viruses when they start a
new therapy.

"The key is to try to ensure that the first regimen is
successful," Dr. Soloway said. To raise the chances of success,
he advises using three agents, including one protease inhibitor;
counseling the patients about how to adhere to a schedule for taking
the drugs; and taking precautions to minimize side effects.

Unfortunately, cross resistance is common among HIV drugs of the same
class, and there are currently only three classes of HIV agents.
"Thats why salvage therapy is less likely to succeed than
the initial therapy," Dr. Soloway said.

Primary care physicians need to take into account several factors
when considering whether to treat HIV patients with antiretroviral
therapy, including the likelihood of disease progression, the
patients lifestyle and attitudes, and any obstacles to
adherence to a drug regimen. Dr. Soloway advises starting treatment
when the HIV viral load is greater than 5,000 copies/mL and the CD4
count is less than 500 cells/mm³.

"If the patient cant adhere to a drug regimen, youre
actually doing more harm than good by treating him," Dr. Soloway
said. "The result of partial treatment, or treatment in which
the patient starts and stops taking the drugs, is the development of
resistant virus."

If the drug therapy does need to be stopped for any reason--say the
patient is pregnant and in the first trimester--all three drugs
should be stopped at the same time, he added.

Providing pregnant women with antiretroviral therapy in the second
and third trimester of pregnancy is beneficial, Dr. Soloway said.
Since 1992 when AZT was first used in pregnancy, the risk of
transmission from HIV-infected mothers to their babies has dropped
from 25% to 8%.

"Theres a clear relationship between viral load and
perinatal transmission," Dr. Soloway said. While acknowledging
that there are no long-term safety studies on the use of these drugs
in pregnancy, he noted that there has, to date, been no evidence of
serious side effects.

Besides treating HIV patients, the primary care provider also needs
to help patients reduce their AIDS risk, Dr. Soloway said. "Keep
in mind the current statistics: Two-thirds of new AIDS patients are
minorities, one-half are heterosexual, and one-third are women."

He pointed out that having another sexually transmitted disease, such
as herpes or gonorrhea, increases a persons risk of sexually
transmitted HIV infection. "We need to emphasize to our patients
that the more sex partners they have, the more they are at risk, and
that condoms should be used in any sexual encounter outside of a
monogamous relationship," Dr. Soloway said.

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